介素-21驱动超代谢状态和CD4+T细胞相关的致病性在慢性肠道炎症
Adebowale O Bamidele1,2, Shravan K Mishra1, Petra Hirsova3
1Immunometabolism and Mucosal Immunity Laboratory, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
bioRxiv : the preprint server for biology
|June 19, 2023
概括
干白素-21 (IL-21) 干扰调节性T细胞 (Treg) 代谢,促进炎症性肠病 (IBD) 的炎症. 针对这种代谢功能障碍可以治疗慢性肠道炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 胃肠病学 胃肠病学
背景情况:
- 无能调节性T细胞 (Tregs) 导致免疫媒介疾病,如炎症性肠病 (IBD).
- 驱动IBD炎症Treg发育和功能的机制尚未完全理解.
- 细胞代谢在Treg功能和肠道平衡中的作用需要研究.
研究的目的:
- 为了研究细胞代谢在调节性T细胞 (Tregs) 中的作用,与肠道平衡相关.
- 了解英尔-21 (IL-21) 如何影响Treg代谢和功能.
- 探索针对IBD中的Treg代谢途径的治疗策略.
主要方法:
- 对人类Tregs进行了线粒体超结构研究,生物化学和蛋白质分析,代谢学和基因表达分析.
- 使用海马XF分析仪进行实时代谢分析,并分析克罗恩氏病单细胞RNA测序数据.
- 在CD4+T细胞诱导的小鼠结肠炎模型中对转基因Tregs的功能评估.
主要成果:
- 介质素-21 (IL-21) 降低了线粒体-ER的对位,导致增强GSK3β活性和Tregs.的高代谢状态.
- 这种IL-21诱导的代谢重新连接放大了Treg炎症反应,这种状态可以通过甲基酸盐 (MePyr) 或GSK3β抑制来逆转.
- 在Tregs中的IL-21诱导的代谢基因在人类克罗恩氏病肠道Tregs中得到了丰富,Il21r-/-Tregs对小鼠结肠炎进行了保护.
结论:
- IL-21触发Tregs中的代谢功能障碍,加剧了它们的炎症反应.
- 准IL-21诱导的Treg代谢为慢性肠道炎症提供了一个潜在的治疗策略.
- 调节Treg代谢可能会减轻CD4+T细胞驱动的肠道炎症.
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